Our current studies on the fluoro derivatives of benzo(rst)pentaphene have contributed to the determination of the active sites of the parent hydrocarbon, where metabolic activation leading to carcinogenesis takes place. The decrease in carcinogenicity by fluorine-substitution at position 3 and its disappearance in the 2,10-difluoro derivative provide evidence for the participation of the bay-region benzo-rings in this metabolic activation. The relative abilities of the compounds to bind with chromatin support this hypothesis. Preliminary NMR studies of the kinetics of deuteriodeprotonation of 2-fluorobenzo(rst)pentaphene suggest that a reactive-free peri position adjacent to the benzo-ring is essential to the process of carcinogenesis. We propose to continue our investigations on the binding of these compounds to chromatin, to study their intercalation with DNA, to determine the rates of D-exchange in the parent carcinogen and its 3-fluoro and 2,10-difluoro derivatives and to test the carcinogenic activity of the compounds by skin application and their mutagenic activity by the Wood-Levin procedure. We also plan to synthesize 5- and 5,8-fluorine-substituted benzo(rst)pentaphene (peri positions) and 7-fluorobenzo(a)pyrene as well as its homologous 4,9-difluorobenzo(rst)pentaphene. We propose to extend our investigations and methodology to the various fluoro derivatives of benzo(a)pyrene and of other important carcinogenic polycyclics as a program for the coming years.